Using advanced technology, the determinants of crossbridge kinetics, force development and chemo-mechanical transduction will be studied in rat trabecular muscle. A model of chronic heart failure secondary to myocardial infarction will be studied. This will be correlated with findings from controls and rats which have been forced, with the induction of hypothyroidism, to express slow myosir isoforms. These studies should provide significant new insights into the fundamental derangements in myofilament function in heart failure. In addition to the wide range of fundamental concepts and controversies regarding contemporary theories of the mechanisms of muscle contraction, the applicant will need to develop a high level of familiarity with the principles of scientific measurement using the complex technology employed in Dr. de Tombe's laboratory.